Functional variants of ERAP1 gene are associated with HLA‐B27 positive spondyloarthritis

Abstract

We investigated two nonsynonymous variants (rs30187 and rs27044) of ERAP1 gene in HLA-B27 positive individuals (150 spondyloarthritis and 108 controls) and in general ankylosing spondylitis (AS) patients (n = 137) vs random controls (n = 139). Both single nucleotide polymorphisms (SNPs) were associated with the risk of spondyloarthritis [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.24-2.62, P = 0.001 for rs30187, OR 1.58, 95% CI 1.07-2.34, P = 0.02 for rs27044]. The CC haplotype was a protective factor (P = 0.002), while the TG haplotype was a risk factor (P = 0.01) for spondyloarthritis. The SNP rs30187 was also associated with the risk of HLA-B27+ AS. For the general group of AS, the carriers of minor alleles showed an increased risk for the disease (OR 1.92, 95% CI 1.17-3.13 for rs30187, OR 1.74, 95% CI 1.08-2.80 for rs27044). This is the first study that shows the association of ERAP1 gene variants and haplotypes with HLA-B27 positive spondyloarthritis.

Association of rs27044 and rs30187 polymorphisms in endoplasmic reticulum aminopeptidase 1 gene and ankylosing spondylitis susceptibility: A meta‐analysis

“…The general characteristics of each eligible study are summarized in Table . Twenty‐six case‐control studies with 31 individual cohorts, containing 17 223 AS patients and 36 915 controls, were included in this meta‐analysis. The eligible studies were published between 2007 and 2019.…”

“…The sample sizes of an individual study ranged from 84 to 3014 for AS patients, and 77 to 20 164 for controls. Thirteen studies were conducted on Europeans, and the remaining 13 studies were performed on Asians . Allele distribution was provided by all included studies, and genotype distribution was provided by 18 studies .…”

Associations between ERAP1 polymorphisms and susceptibility to ankylosing spondylitis: a meta-analysis

“…A previous genome-wide association study revealed that ERAP1 polymorphisms are associated with AS at a high level of statistical significance [3], but more recent studies, in different ethnic groups, have produced mixed results [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. In our previous meta-analysis, we found that the rs27044, rs17482078, rs10050860, rs30187, and rs2287987 polymorphisms of ERAP1 were associated with the development of AS in Europeans [28].…”

“…Two studies were excluded because one used the data analyzed in another study and another did not have extractable allele data. Thus, 20 studies met the inclusion criteria (Table 1) [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]27]. However, one of these studies contained data on three groups [13] and two studies had data on two different groups [17].…”

“…A genome-wide association study revealed that two single-nucleotide polymorphisms (SNPs) (rs27044, rs30187) of ERAP1 were significantly associated with AS, and demonstrated that rs17482078, rs10050860, and rs2287987 polymorphisms also trended toward association with AS [3]. Although some studies have demonstrated that SNPs of ERAP1 are associated with AS susceptibility, others disagree [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. It would appear that allelic frequencies often differ substantially between populations, and ethnicity-specific association studies are needed to confirm genetic associations in different populations.…”